Anti-Nogo antibody
Currently in the early stages of clinical investigation. One first-in-human study found the human anti-Nogo-A antibody ATI355 was well tolerated in patients with acute, complete traumatic paraplegia and tetraplegia.[141]Kucher K, Johns D, Maier D, et al. First-in-man intrathecal application of neurite growth-promoting anti-Nogo-A antibodies in acute spinal cord injury. Neurorehabil Neural Repair. 2018 Jun;32(6-7):578-89.
https://journals.sagepub.com/doi/10.1177/1545968318776371
http://www.ncbi.nlm.nih.gov/pubmed/29869587?tool=bestpractice.com
A phase 2 trial is ongoing.[142]ClinicalTrials.gov. NISCI - Nogo inhibition in spinal cord injury (NISCI). Oct 2021 [internet publication].
https://www.clinicaltrials.gov/ct2/show/NCT03935321
Riluzole
Exerts a potentially protective effect on white matter by blocking the influx of sodium into damaged cells.[143]Kwon BK, Sekhon LH, Fehlings MG. Emerging repair, regeneration, and translational research advances for spinal cord injury. Spine (Phila Pa 1976). 2010 Oct 1;35(21 suppl):S263-70.
http://www.ncbi.nlm.nih.gov/pubmed/20881470?tool=bestpractice.com
Two phase 1 trials in acute spinal cord injury have completed, and one phase 2/3 trial was initiated but terminated early due to slow enrollment.[144]Chow DS, Teng Y, Toups EG, et al. Pharmacology of riluzole in acute spinal cord injury. J Neurosurg Spine. 2012 Sep;17(1 suppl):129-40.
http://www.ncbi.nlm.nih.gov/pubmed/22985379?tool=bestpractice.com
[145]Grossman RG, Fehlings MG, Frankowski RF, et al. A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury. J Neurotrauma. 2014 Feb 1;31(3):239-55.
https://www.liebertpub.com/doi/10.1089/neu.2013.2969
http://www.ncbi.nlm.nih.gov/pubmed/23859435?tool=bestpractice.com
[146]Fehlings MG, Nakashima H, Nagoshi N, et al. Rationale, design and critical end points for the Riluzole in Acute Spinal Cord Injury Study (RISCIS): a randomized, double-blinded, placebo-controlled parallel multi-center trial. Spinal Cord. 2016 Jan;54(1):8-15.
https://www.nature.com/articles/sc201595
http://www.ncbi.nlm.nih.gov/pubmed/26099215?tool=bestpractice.com
[147]ClinicalTrials.gov. Riluzole in spinal cord injury study (RISCIS). Apr 2021 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT01597518
Minocycline
A tetracycline antibiotic that has been found to attenuate neuroinflammation, inhibit apoptosis, and prevent neuronal damage.[143]Kwon BK, Sekhon LH, Fehlings MG. Emerging repair, regeneration, and translational research advances for spinal cord injury. Spine (Phila Pa 1976). 2010 Oct 1;35(21 suppl):S263-70.
http://www.ncbi.nlm.nih.gov/pubmed/20881470?tool=bestpractice.com
In one phase 2 clinical trial, patients receiving minocycline experienced greater motor recovery than those receiving placebo; a phase 3 trial is ongoing.[148]ClinicalTrials.gov. Minocycline in acute spinal cord injury (MASC). Oct 2014 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT01828203
[149]Casha S, Zygun D, McGowan MD, et al. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain. 2012 Apr;135(Pt 4):1224-36.
https://academic.oup.com/brain/article/135/4/1224/362413
http://www.ncbi.nlm.nih.gov/pubmed/22505632?tool=bestpractice.com
Cethrin
A bacterial-derived toxin (BA-210) combined with a hemostatic adhesive, cethrin improved motor function in one phase 1/2a trial of patients with thoracic or cervical spinal cord injury.[150]Fehlings MG, Theodore N, Harrop J, et al. A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. J Neurotrauma. 2011 May;28(5):787-96.
http://www.ncbi.nlm.nih.gov/pubmed/21381984?tool=bestpractice.com
Further clinical trials are planned.
Basic fibroblast growth factor (basic FGF)
It has been hypothesized that basic FGF might improve functional and respiratory parameters, presumably by reducing glutamate-mediated excitotoxicity. One phase 1/2 trial of basic FGF injection at the site of injury is ongoing.
Neuromodulation
There is some evidence to suggest that neuromodulation can aid rehabilitation efforts.[151]Harkema S, Gerasimenko Y, Hodes J, et al. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet. 2011 Jun 4;377(9781):1938-47.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154251
http://www.ncbi.nlm.nih.gov/pubmed/21601270?tool=bestpractice.com
One phase 2 trial is ongoing.[152]ClinicalTrials.gov. Neuromodulation techniques after SCI. Apr 2021 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT04241250
Stem-cell therapy
Bone marrow-derived stem cells appeared to improve bladder function, quality of life, and motor function in small studies of patients with spinal cord injury.[153]Geffner LF, Santacruz P, Izurieta M, et al. Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell Transplant. 2008;17(12):1277-93.
http://www.ncbi.nlm.nih.gov/pubmed/19364066?tool=bestpractice.com
[154]Yoon SH, Shim YS, Park YH, et al. Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: phase I/II clinical trial. Stem Cells. 2007 Aug;25(8):2066-73.
https://academic.oup.com/stmcls/article/25/8/2066/6402489
http://www.ncbi.nlm.nih.gov/pubmed/17464087?tool=bestpractice.com
Some patients treated with activated autologous macrophages or olfactory ensheathing cells experienced modest motor improvement, but results were inconsistent.[155]Knoller N, Auerbach G, Fulga V, et al. Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine. 2005 Sep;3(3):173-81.
http://www.ncbi.nlm.nih.gov/pubmed/16235699?tool=bestpractice.com
[156]Lammertse DP, Jones LA, Charlifue SB, et al. Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial. Spinal Cord. 2012 Sep;50(9):661-71.
http://www.ncbi.nlm.nih.gov/pubmed/22525310?tool=bestpractice.com
[157]Lima C, Escada P, Pratas-Vital J, et al. Olfactory mucosal autografts and rehabilitation for chronic traumatic spinal cord injury. Neurorehabil Neural Repair. 2010 Jan;24(1):10-22.
http://www.ncbi.nlm.nih.gov/pubmed/19794133?tool=bestpractice.com